The Immunodominant, Ld-Restricted T Cell Response to Hepatitis B Surface Antigen (HBsAg) Efficiently Suppresses T Cell Priming to Multiple Dd-, Kd-, and Kb-Restricted HBsAg Epitopes

Abstract

MHC-I-restricted CTL responses of H-2d (Ld+ or Ld−) and F1 H-2dxb mice to hepatitis B surface Ag (HBsAg) are primed by either DNA vaccines or HBsAg particles. The Dd/S201–209 and Kd/S199–208 epitopes are generated by processing endogenous HBsAg; the Kb/S208–215 epitope is generated by processing exogenous HBsAg; and the Ld/S28–39 epitope is generated by exogenous as well as endogenous processing of HBsAg. DNA vaccination primed high numbers of CTL specific for the Ld/S28–39 HBsAg epitope, low numbers of CTL specific for the Dd/S201–209 or Kd/S199–208 HBsAg epitopes in BALB/c mice, and high numbers of Dd/S201–209- and Kd/S199–208-specific CTL in congenic H-2d/Ld− dm2 mice. In F1dxb mice, the Kd-, Dd-, and Kb-restricted CTL responses to HBsAg were strikingly suppressed in the presence but efficiently elicited in the absence of Ld/S28–39-specific CTL. Once primed, the Kd- and Dd-restricted CTL responses to HBsAg were resistant to suppression by immunodominant Ld/S28–39-specific CTL. The Ld-restricted immunodominant CTL reactivity to HBsAg can thus suppress priming to multiple alternative epitopes of HBsAg, independent of the processing pathway that generates the epitope, of the background of the mouse strain used, and of the presence/absence of different allelic variants of the K and D MHC class I molecules.

The Immunodominant CD8 T Cell Response to the Human Cytomegalovirus Tegument Phosphoprotein pp65495–503 Epitope Critically Depends on CD4 T Cell Help in Vaccinated HLA-A*0201 Transgenic Mice

“…3C). The number of immunodominant CD8 T cells is apparently not important to suppress subdominant immune responses, confirming our previous reports in an HBV model (55,56).…”

“…However, interference between responses to individual epitopes presented by the same or different MHC class I molecules is the well-established phenomenon of immunodominance that limits the repertoire diversity of CD8 T cell responses primed by such vaccines (18,19). We have shown that immunodominance hierarchies operate in CD8 T cell responses to different epitopes of the same Ag, between different Ags of the same virus, or between unrelated Ags (50,55,56,62,63). (56).…”

“…We complexed immunostimulatory ODNs to short, synthetic peptides in which the cationic HIV-tat [49][50][51][52][53][54][55][56][57] RKKRRQRRR domain (tat) was fused NH 2 terminally to the antigenic e6, e3, and e8 epitopes (47). This generated the cationic tat/e3 (tat-LMNGQQIFL), tat/e6 (tat-NLVPMVATV), and tat/e8 (tat-RIFAELGEV) peptides.…”

CD8 T cell competition for dendritic cellsin vivois an early event in activation

“…It is important to consider, however, that the dominance of a particular epitope is not necessarily linked to the abundance of the epitope on the surface of the APC (26) and that the absence of an epitope or MHC molecule can lead to the conversion of a subdominant epitope to a dominant epitope (27,28). The results described here show that CD8 T cell immunodominance caused by competition between T cell clones for DCs can occur in the first few hours of a response.…”

Asynchronous Differentiation of CD8 T Cells That Recognize Dominant and Cryptic Antigens

“…Strikingly, under the latter circumstances, CD8 T cells respond to only a few immunodominant epitopes and neglect other potentially immunogenic peptides (cryptic epitopes). Restriction of CD8 T cell responses to a few selected epitopes has been termed immunodominance, a central and robust feature of immune responses (1)(2)(3)(4)(5)(6)(7)(8). At face value, immunodominance is counterintuitive.…”